Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease

Amit V. Khera, M.D., Connor A. Emdin, D.Phil., Isabel Drake, Ph.D., Pradeep Natarajan, M.D., Alexander G. Bick, M.D., Ph.D., Nancy R. Cook, Ph.D., Daniel I. Chasman, Ph.D., Usman Baber, M.D., Roxana Mehran, M.D., Daniel J. Rader, M.D., Valentin Fuster, M.D., Ph.D., Eric Boerwinkle, Ph.D., Olle Melander, M.D., Ph.D., Marju Orho-Melander, Ph.D., Paul M Ridker, M.D., … Read more

Genetics of coronary artery disease: discovery, biology and clinical translation

Khera AV, Kathiresan S. Coronary artery disease is the leading global cause of mortality. Long recognized to be heritable, recent advances have started to unravel the genetic architecture of the disease. Common variant association studies have linked approximately 60 genetic loci to coronary risk. Large-scale gene sequencing efforts and functional studies have facilitated a better … Read more

Is Coronary Atherosclerosis One Disease or Many?

Khera AV, Kathiresan S. Although a small subset of the population may have a dominant driving pathway, we believe a quantitative blend of causal genetic and environmental factors underlies the majority of CAD cases. An expectation of a taxonomic revolution in complex disease derived from precision medicine efforts may lead to failure in the eyes … Read more

ANGPTL3 Deficiency and Protection Against Coronary Artery Disease

Nathan O. Stitziel, MD, PHD, Amit V. Khera, MD, Xiao Wang, PHD, Andrew J. Bierhals, MD, MPH, A. Christina Vourakis, BA, Alexandra E. Sperry, BA, Pradeep Natarajan, MD, Derek Klarin, MD, Connor A. Emdin, DPHIL, Seyedeh M. Zekavat, BSc, Akihiro Nomura, MD, Jeanette Erdmann, PHD, Heribert Schunkert, MD, Nilesh J. Samani, MD,m,n William E. Kraus, … Read more

Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity

Danish Saleheen, Pradeep Natarajan, Irina M. Armean, Wei Zhao, Asif Rasheed, Sumeet A. Khetarpal, Hong-Hee Won, Konrad J. Karczewski. Anne H. O’Donnell-Luria, Kaitlin E. Samocha, Benjamin Weisburd, Namrata Gupta, Mozzam Zaidi, Maria Samuel, Atif Imran, Shahid Abbas, Faisal Majeed, Madiha Ishaq, Saba Akhtar, Kevin Trindade, Megan Mucksavage, Nadeem Qamar, Khan Shah Zaman, Zia Yaqoob, Tahir … Read more

Cardiovascular endocrinology: Is ANGPTL3 the next PCSK9?

Is ANGPTL3 the next PCSK9? Recent reports suggest that molecular therapies targeting ANGPTL3 and its encoded protein angiopoietin-like protein 3 have clinical potential comparable to therapies targeting PCSK9 and its encoded protein proprotein convertase subtilisin/kexin type 9. By mainly affecting triglyceride-rich lipoproteins, ANGPTL3 inhibition might prove complementary to LDL cholesterol lowering with PCSK9 blockade.

A Genetic Variant Associated with Five Vascular Diseases Is a Distal Regulator of Endothelin-1 Gene Expression

Genome-wide association studies (GWASs) implicate the PHACTR1 locus (6p24) in risk for five vascular diseases, including coronary artery disease, migraine headache, cervical artery dissection, fibromuscular dysplasia, and hypertension. Through genetic fine mapping, we prioritized rs9349379, a common SNP in the third intron of the PHACTR1 gene, as the putative causal variant. Epigenomic data from human … Read more